Enantioselective Total Synthesis of (‐)‐Finerenone using Asymmetric Transfer Hydrogenation

(−)‐Finerenone is a nonsteroidal mineralocorticoid receptor antagonist currently in phase III clinical trials for the treatment of chronic kidney disease in type 2 diabetes. It contains an unusual dihydronaphthyridine core. We report a 6‐step synthesis of (−)‐finerenone, which features an enantioselective partial transfer hydrogenation of a naphthyridine using a chiral phosphoric acid catalyst with a Hantzsch ester. The process is complicated by the fact that the naphthyridine exists as a mixture of two atropisomers that react at different rates and with different selectivities. The intrinsic kinetic resolution was converted into a kinetic dynamic resolution at elevated temperature, which enabled us to obtain (−)‐finerenone in both high yield and high enantioselectivity. DFT calculations have revealed the origin of selectivity.<br/

Six-membered ring systems: with O and/or S atoms

A large variety of publications involving O- and S-6-membered ring systems have appeared in 2017. The importance of these heterocyclic compounds is highlighted by the huge number of publications on the total synthesis of natural oxygen derivatives and of other communications dedicated to synthetic derivatives. Reviews on stereoselective organocatalytic synthesis of tetrahydropyrans (17EJO4666), of tetrahydropyrans and their application in total synthesis of natural products (17CSR1661), on the synthesis of the less thermodynamically stable 2,6-trans-tetrahydropyrans (17S4899), on enantioselective synthesis of polyfunctionalized pyran and chromene derivatives (17TA1462), and on enantioselective and racemic total synthesis of camptothecins, including the formation of their pyran-2-one ring (17SL1134), have appeared. Advances in the transition metal-catalyzed synthesis of pyran-2/4-ones (17TL263), N-heterocyclic carbene (NHC)-catalyzed achiral synthesis of pyran-2-one, coumarin and (thio)chromone derivatives (17OBC4731), on the synthesis and transformation of 2H-pyran-2-ones (17T2529) and 2-styrylchromones (17EJO3115) into other heterocyclic compounds, have been surveyed. The strategies to build up the tetrahydropyranyl core of brevisamide (17H(95)81) and the reactions of ketyl radicals, generated from carbonyl derivatives under transition-metal photoredox-catalyzed conditions, leading to isochromen- and chroman-type compounds (17CC13093) were disclosed. Developments in the synthesis of pentafluorosulfanyl(chromene and coumarin) derivatives (17TL4803), photoswitchable D9-tetrahydrocannabinol derivatives (17JA18206), and aminobenzopyranoxanthenes with nitrogen-containing rings (17JOC13626) have been studied.info:eu-repo/semantics/publishedVersio

Borane-Catalyzed Ring-Opening and Ring-Closing Cascades of Furans Leading to Silicon-Functionalized Synthetic Intermediates

The conversion of renewable biomass resources to synthetically valuable chemicals is highly desirable, but remains a formidable challenge in regards to the substrate scope and reaction conditions. Here we present the development of tris(pentafluorophenyl)borane–catalysed conversion of furans via ring-opening and closing cascade processes to afford siliconfunctionalized synthetic chemicals under transition metal-free conditions. The furan ring-opening with hydrosilanes is highly efficient (TON up to 2,000) and atom-economical without forming any byproduct to give rise to a-silyloxy-(Z)-alkenyl silanes. Additional equivalents of silane smoothly induce a subsequent B(C6F5)3-catalysed cyclization of initially formed olefinic silane compounds to produce anti-(2-alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable in the synthesis of natural products and pharmacophores. (c) The Author(s) 201611sciescopu

Selective Silylative Reduction of Pyridines Leading to Structurally Diverse Azacyclic Compounds with the Formation of sp3 C-Si Bonds

Tris(pentafluorophenyl)borane-catalyzed silylative reduction of pyridines has been developed giving rise to the formation of sp3 C-Si bonds selectively beta to the nitrogen atom of azacyclic products. Depending on the position and nature of pyridine substituents, structurally diverse azacycles are obtained with high selectivity under the borane catalysis. Mechanistic studies elucidated the sequence of hydrosilylation in this multiple reduction cascade: 1,2- or 1,4-hydrosilylation as an initial step depending on the substituent position, followed by selective hydrosilylation of enamine double bonds eventually affording β-silylated azacyclic compounds. © 2015 American Chemical Society133321sciescopu

Boron-Catalyzed Hydrogenative Reduction of Substituted Quinolines to Tetrahydroquinolines with Hydrosilanes

A metal-free procedure for the hydrogenative reduction of substituted N-heteroaromatics has been developed by using hydrosilanes as reducing agents. The optimized conditions were successfully applied to the reactions of quinolines, quinoxalines, and quinoline N -oxides. They were also effective for the reduction of quinolines bearing amino or hydroxy groups, where H 2 was evolved through dehydrogenative silylation of the amine or hydroxy moieties. Preliminary mechanistic studies revealed that the initial step in the catalytic cycle involves 1,4-addition of the hydrosilane to the quinoline to give a 1,4-dihydroquinoline; this is followed by (transfer) hydrogenation to deliver the tetrahydroquinoline as the final product. © Georg Thieme Verlag Stuttgart.New York1331sciescopu

Borane catalysed ring opening and closing cascades of furans leading to silicon functionalized synthetic intermediates

The conversion of renewable biomass resources to synthetically valuable chemicals is highly desirable, but remains a formidable challenge in regards to the substrate scope and reaction conditions. Here we present the development of tris(pentafluorophenyl)borane-catalysed conversion of furans via ring-opening and closing cascade processes to afford silicon-functionalized synthetic chemicals under transition metal-free conditions. The furan ring-opening with hydrosilanes is highly efficient (TON up to 2,000) and atom-economical without forming any byproduct to give rise to α-silyloxy-(Z)-alkenyl silanes. Additional equivalents of silane smoothly induce a subsequent B(C6 F5)3 -catalysed cyclization of initially formed olefinic silane compounds to produce anti-(2-alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable in the synthesis of natural products and pharmacophores. © The Author(s) 2016113121sciescopu

Selective Silylative Reduction of Pyridines Leading to Structurally Diverse Azacyclic Compounds with the Formation of sp³ C–Si Bonds

Tris­(pentafluorophenyl)­borane-catalyzed silylative reduction of pyridines has been developed giving rise to the formation of sp³ C–Si bonds selectively beta to the nitrogen atom of azacyclic products. Depending on the position and nature of pyridine substituents, structurally diverse azacycles are obtained with high selectivity under the borane catalysis. Mechanistic studies elucidated the sequence of hydrosilylation in this multiple reduction cascade: 1,2- or 1,4-hydrosilylation as an initial step depending on the substituent position, followed by selective hydrosilylation of enamine double bonds eventually affording β-silylated azacyclic compounds